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Genome-Wide Mapping of Collier In Vivo Binding Sites Highlights Its Hierarchical Position in Different Transcription Regulatory Networks

机译:体内结合位点的全基因组定位突显了其在不同转录调控网络中的分层位置

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摘要

Collier, the single Drosophila COE (Collier/EBF/Olf-1) transcription factor, is required in several developmental processes, including head patterning and specification of muscle and neuron identity during embryogenesis. To identify direct Collier (Col) targets in different cell types, we used ChIP-seq to map Col binding sites throughout the genome, at mid-embryogenesis. In vivo Col binding peaks were associated to 415 potential direct target genes. Gene Ontology analysis revealed a strong enrichment in proteins with DNA binding and/or transcription-regulatory properties. Characterization of a selection of candidates, using transgenic CRM-reporter assays, identified direct Col targets in dorso-lateral somatic muscles and specific neuron types in the central nervous system. These data brought new evidence that Col direct control of the expression of the transcription regulators apterous and eyes-absent (eya) is critical to specifying neuronal identities. They also showed that cross-regulation between col and eya in muscle progenitor cells is required for specification of muscle identity, revealing a new parallel between the myogenic regulatory networks operating in Drosophila and vertebrates. Col regulation of eya, both in specific muscle and neuronal lineages, may illustrate one mechanism behind the evolutionary diversification of Col biological roles.
机译:Collier是单个果蝇COE(Collier / EBF / Olf-1)转录因子,在几个发育过程中都需要,包括头部形成以及胚胎发生过程中肌肉和神经元身份的指定。为了鉴定不同细胞类型中的直接Collier(Col)靶标,我们在胚胎发生中期使用ChIP-seq绘制了整个基因组中Col结合位点的图谱。体内Col结合峰与415个潜在的直接靶基因相关。基因本体分析显示具有DNA结合和/或转录调节特性的蛋白质大量富集。使用转基因CRM报告者测定法对候选物进行表征,确定了背外侧躯体肌肉中的直接Col靶标和中枢神经系统中的特定神经元类型。这些数据带来了新的证据,表明Col对特有和无眼(eya)转录调节因子的表达的直接控制对于指定神经元身份至关重要。他们还表明,肌肉祖细胞中col和eya之间的交叉调节对于规范肌肉的身份是必需的,这揭示了果蝇和脊椎动物的肌源性调节网络之间的新相似之处。在特定的肌肉和神经元谱系中,大麦的Col调节可能说明了Col生物学角色进化多样化背后的一种机制。

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